Updated results from a study with the OncoDefender-CRC assay (Everist Genomics), a molecular prognostic test for early-stage colorectal cancer patients, will be presented at the 47th American Society of Clinical Oncology (ASCO) Annual Meeting, which will be held June 3-7, 2011, in Chicago.

Colorectal cancer is one of the major causes of cancer death worldwide, accounting for more than 150,000 new cases and 55,000 deaths in the United States every year and 125,000 deaths each year in Europe.[1] To date, surgery, followed by adjuvant chemotherapy when appropriate, is the mainstay of therapy for patients with localized disease. Of the estimated 68,000 patients that will be diagnosed with early stage colorectal cancer this year in the US, approximately 15% of stage I patients and 30% of stage II patients will recur following curative surgery. Many of these latter patients may have been cured or had their lives prolonged had they been more accurately identified as being at ‘high-risk’ for tumor recurrence and received post-surgical resection adjuvant therapy. Identifying those patients at high-risk for colorectal cancer recurrence can reduce mortality, morbidity and cost of care.

Predicting risk of recurrence
The assay, which is the only molecular prognostic test capable of accurately predicting risk of recurrence of cancer in patients previously treated with surgical resection of a Stage I/II colon cancer tumor or Stage I rectal cancer tumor, examines expression levels of a panel of genes extracted from formalin-fixed paraffin-embedded cancer tissue taken at the time of surgery, and uses a proprietary computer-generated decision rule to stratify patients into ‘high-risk’ and ‘low-risk’ categories for assessing likelihood of recurrence.

Accurately identifying Stage I/II colorectal cancer patients who are at risk of recurrence represents a significant unmet medical need as mortality rates for early stage disease are higher than generally realized. “About one in seven patients with Stage I and one in three patients with Stage II colorectal cancer will ultimately experience a recurrence,” said Peter F. Lenehan, M.D., Ph.D. Chief Medical Officer of Everist Genomics. “In this sub-population of patients who recur, the associated mortality rates are 50% and 80%, respectively.”

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Differentiating between patients
The study confirmed that OncoDefender-CRC was able to differentiate those patients at high risk from those at low risk for cancer recurrence within 3 years after potentially curative surgery more accurately than assessments based on National Comprehensive Cancer Network (NCCN) Guidelines, widely accepted as providing “best practices” in oncology. The study included patient samples from four international sites.

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For stages I/II colorectal cancer (n=115), OncoDefender-CRC correctly classified 32/46 cases of recurrence and 38/69 cases of non-recurrence (sensitivity 70%, specificity 55%). ‘High-risk’ patients had a significantly higher probability of recurrence within 36 months than ‘low-risk’ patients (PPV 0.51, NPV 0.73, HR 2.06 (95% CI: 1.10 to 3.86; p=0.020)). In contrast, the standard prognostic guidelines described by the NCCN Guidelines were unable to differentiate recurrence risk in this population (p=0.315).

The study found that Stage I colorectal cancer patients that were deemed ‘high-risk’ by the test recurred at a rate more than triple that for patients deemed ‘low-risk’. “The updated data demonstrate that OncoDefender-CRC provides a more targeted stratification of patients, independent of other recognized prognostic variables, such as age, T-stage, grade, tumor location and lymphovascular invasion,” Lenehan noted.

Recent research in cancer genomics has shown that Stage I/II colorectal cancer tumors can differ greatly from other tumors that are classified in the same stage, indicating that some tumors present observable high-risk characteristics. Tumors that present such high-risk characteristics can be more than 20 times more likely to lead to a recurrence than tumors with low-risk characteristics. By more accurately identifying patients who have high-risk tumors, Lenehan said healthcare providers can more effectively target their treatment decisions, thereby potentially improving clinical outcomes.

“Recent literature shows that patients identified with high-risk early stage tumors benefit significantly from surgical removal of the tumor followed by adjuvant therapy,” Lenehan said. “Until recently, however, physicians have not been equipped with prognostic tests that can accurately distinguish high-risk early stage tumors from low-risk tumors.”

“The data from the OncoDefender-CRC study validate the effectiveness of this node-negative prognostic test in determining recurrence risk for this population, demonstrating the potential for optimizing post-op clinical management and patient stratification in therapeutic clinical trials,” he concluded.

For more information:
[1] Wolpin BM, Meyerhardt JA, Mamon HJ, Mayer RJ. Adjuvant treatment of colorectal cancer. Cancer J Clin 57:168?185, 2007.

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